Integrins are a family of adhesion receptors (reviewed in Ruoslahti and Pierschbacher, Science, 238:491-497, 1987). An integrin molecule is a heterodimeric membrane protein composed of one .alpha. subunit and one .beta. subunit. Several subunits of each kind are known, and various combinations of these subunits make up receptors with different ligand specificities. The ligands for integrins are extracellular matrix proteins such as fibronectin, laminin, collagens and vitronectin or membrane proteins at the surface of other cells.
By binding to their ligands, integrins mediate the adhesion of cells to extracellular matrices and other cells. Adhesion is important for a cell. It provides anchorage, traction for migration, signals for homing, and regulates growth and differentiation of cells.
There are a number of instances where it is important to determine the complement of adhesion receptors possessed by cells. For example, it has been shown that inhibition of the fibronectin receptor function by synthetic peptides that bind to this receptor prevents tumor cells (Gehlsen et al., J. Cell. Biol., 106:925-930, 1988) or lymphocytes (Thiery et al., Ann. Rev. Cell. Biol., 1:91-113, 1985) from invading and migrating through tissues. In contrast, inhibition of the function of another integrin, the vitronectin receptor, has no effect on tumor cell migration (Gehlsen et al., op cit.). Thus, it would be important to determine whether a tumor has fibronectin receptors to assess the potential susceptibility of its invasive properties to inhibitors of this receptor. Similar considerations apply to the laminin receptors, which are also thought to play a role in invasion (Gehlsen et al., Science 241:1228-1229, 1988).
Another situation in which determination of the integrins possessed by cells is important, is when the tissue of origin of a tumor is analyzed. Tissue-specific markers have proven to be a very useful adjunct for such an analysis in the clinical pathology setting. Some of the integrins are tissue-specific in their expression, providing potentially useful markers for the diagnosis of tumor origin. Thus, for example, the primary platelet integrin gp IIb/IIIa is restricted to platelets and leukemia cells capable of expressing megakaryocytic properties (in BIOCHEMISTRY OF PLATELETS, D. R. Phillips and M. A. Schuman, Eds., Academic Press, N.Y., 1986; Suzuki et al., J. Biol. Chem. 262:14080-14085, 1987). As is the case with most other cellular markers, the detection of integrins in cells and tissues is best accomplished with antibodies.
There thus exists a need for antibodies specific to various integrins. This invention satisfies this need by providing a simple and reproducible method for the preparation of anti-integrin antibodies suitable for the detection and quantitation of integrins by immunoassays.